Dystrophin is the scaffold of a protein complex, disrupted in inherited muscular dystrophies. At the last 3' terminus of the gene, a protein domain is encoded, where syntrophins are tightly hound. These are a family of cytoplasmic peripheral membrane proteins. Three genes have been described encoding one acidic (α1) and two basic (β1 and β2) proteins of 57-60 kDa. Here, we describe the characterization of two novel putative members of the syntrophin family, named γ1- and γ2-syntrophins. The human γ1-syntrophin gene is composed of 19 exons and encodes a brain-specific protein of 517 amino acids. The human γ2-syntrophin gene is composed of at least 17 exons, and its transcript is expressed in brain and, to a lesser degree, in other tissues. We mapped the γ1-syntrophin gene to human chromosome 8q11 and the γ2-syntrophin gene to chromosome 2p25. Yeast two-hybrid experiments and pull-down studies showed that both proteins can bind the C-terminal region of dystrophin and related proteins. We raised antibodies against these proteins and recognized expression in both rat and human central neurons, coincident with RNA in situ hybridization of adjacent sections. Our present findings suggest a differentiated role of a modified dystrophin-associated complex in the central nervous system.
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